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Synthesis, Characterization, In Silico Analysis, and Pharmacological Evaluation of Metoprolol-Modified Saccharide Conjugates for Cardiovascular Targeting

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Abstract

Targeted drug delivery to selective cell has emerged as one of the most significant areas of biomedical engineering research today, so to optimize the therapeutic efficacy of a drug by localizing strictly its pharmacological action to a pathophysiologically relevant tissue system. The current study is aimed to develop saccharide conjugates for targeted delivery of metoprolol, the cardio-selective β-blocker. The examination was done in two significant steps. The initial step includes synthesis of modified saccharides (MS). These MS were used for synthesis of metoprolol-modified saccharide conjugates (MET-MS). The chemical modification of saccharides was evaluated for its swellability and HLB followed by FTIR and DSC. The affirmation of conjugate synthesis was finished by melting point and TLC as primary parameters followed by HR-MS, FTIR, DSC, and [1] H NMR study. Drug release analysis and cellular uptake study examination were completed utilizing H9c2 cell lines. Brine shrimp lethality bioassay was done to research the cytotoxicity of synthesized conjugates. The rate lethality and LC50 values were dictated by contrasting the mean enduring hatchlings of the test and control tubes. In silico examination was performed to evaluate the possible binding of the developed conjugates with the GLUT-4. Homology model of the GLUT-4 was created utilizing SWISS MODEL server.

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Acknowledgements

Authors are thankful to the Principal, Ashokrao Mane College of Pharmacy, Peth Vadgaon, for providing facility to carry out this research project. Authors are thankful to Principal, DSTS Mandal’s College of Pharmacy, Solapur, and Bharati Vidyapeeth College of Pharmacy, Kolhapur, for supporting this research work.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, DSTS Mandal’s College of Pharmacy, Solapur, Maharashtra, India

    Smita Tukaram Kumbhar

  2. Department of Pharmaceutics, Ashokrao Mane College of Pharmacy, Peth Vadgaon, India

    Shitalkumar Shivgonda Patil

  3. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India

    Manish Sudesh Bhatia

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  1. Smita Tukaram Kumbhar
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  2. Shitalkumar Shivgonda Patil
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Correspondence to Smita Tukaram Kumbhar.

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Kumbhar, S.T., Patil, S.S. & Bhatia, M.S. Synthesis, Characterization, In Silico Analysis, and Pharmacological Evaluation of Metoprolol-Modified Saccharide Conjugates for Cardiovascular Targeting. J Pharm Innov 17, 921–930 (2022). https://doi.org/10.1007/s12247-021-09574-1

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